| Autor: |
Rebecca E. Tweedell, Rhoel R. Dinglasan, Sandrine E. Nsango, Prachi Khare, Randall F. Howard, Ronald R. Cobb, Borja López-Gutiérrez, Juan Daniel Martínez, Timothy Hamerly, Nicole G Bender, Eric M. Vela, Abhai K. Tripathi, Vincent O. Nyasembe, Dustin Miller, Matthias Harbers |
| Rok vydání: |
2020 |
| Předmět: |
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| Popis: |
Malaria transmission-blocking vaccines (TBVs) are a critical tool for disease elimination. TBVs prevent completion of the developmental lifecycle of malarial parasites within the mosquito vector, effectively blocking subsequent infections. The mosquito midgut protein Anopheline alanyl aminopeptidase N (AnAPN1) is the leading, mosquito-based TBV antigen and structure-function studies have identified two Class II epitopes that induce potent transmission-blocking (T-B) antibodies. Here, we functionally screened new immunogens and down-selected to the UF6b construct that has two glycine-linked copies of the T-B epitopes. We established a process for manufacturing UF6b and evaluated in outbred female CD1 mice the immunogenicity of the preclinical product with the human-safe adjuvant Glucopyranosyl Lipid Adjuvant in a liposomal formulation with saponin QS21 (GLA-LSQ). UF6b:GLA-LSQ was immunogenic and immunofocused the humoral response to one of the key T-B epitopes resulting in potent T-B activity and establishing UF6b as a prime TBV candidate to aid in malaria elimination and eradication efforts. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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